This invention relates generally to methods and systems for medical treatment of the human body, and more specifically relates to a method and system usable in treating the blood supply of a human subject for the purpose of reducing the functioning lymphocyte population in the blood supply of such subject.
In a number of highly significant human diseases, including certain forms of leukemia, the population of certain types of leucocytes, including especially lymphocytes, increases inordinately in comparison to the other populations of nucleated cells in normal blood. While the excessive population of such lymphocytes represents a result of, rather than the underlying cause of the disease, the excessive lymphocyte population brings direct adverse effects to the patient if steps are not taken to reduce same. Complications thus rapidly develop which impair function of bodily organs, and eventually a life-threatening situation is presented.
It should also be appreciated that excessive increase in the lymphocyte population of the blood supply can occur in other human maladies, in addition to lymphocytic leukemias. Thus, for example, such results can obtain in consequence of severe allergic reactions to administered agents, including drugs or the like, or in many other lymphocyte-mediated diseases.
In addition to the development over the years of pharmaceutical agents and the like, which may nonspecifically reduce the lymphocyte population, e.g. by altering the underlying production rate of same, various techniques have from time to time been used in an effort to directly attack the problem, as for example by mechanically removing such lymphocytes from the blood supply. It is thus known, for example, to pass the blood supply through a continuous centrifuge, whereat one seeks to selectively remove lymphocytes to reduce the population of the latter in the thereby processed blood supply. In general, however, this method tends to be very inefficient, in part because the density differences between the blood fractions including the undesired lymphocytes and fractions which include desired blood components, is insufficient to assure that high percentages of the former are removed while retaining high proportions of the latter.
It is also well-known to treat diseases such as leukemia with high energy electromagnetic radiation, including in the X-ray region. While such treatment is often directed at internal bodily organs whereat the blood cells are being generated, it has also been known to irradiate the blood supply with x-radiation at a point external to the body (the blood having first been withdrawn), whereby the radiation is not rendered directly incident on the body or internal organs of same. This method, while powerful, is indiscriminate, in that the intensely disruptive energy, in addition to destroying undesirable cells, disables or destroys components of the blood which are desired to be retained in vital status.
For many years, it has been known that certain heterocyclic furocoumarins possess photoactive properties that render same useful in the treatment of certain human diseases. A noteworthy example of this occurs in certain recently reported methods for treatment of psoriasis.
The photoactive compounds referred to are all members of a group of coumarin derivatives which are commonly referred to as "psoralens", the basic member of which is the (photoactive) compound psoralen, having the structure: ##STR1##
The remaining compounds of interest for this invention (as will be discussed in greater detail hereinbelow) are all derivatives of psoralen, i.e. of structure (1). In accordance, however, with accepted terminology in the nomenclature of the pertinent chemical art, the phrase "psoralen" or "a psoralen" will be used at places in this specification to refer to certain derivatives of structure (1) which include "psoralen" in their accepted name, such as 8-methoxypsoralen, 5-methoxypsoralen, etc.
In an article appearing in the New England Journal of Medicine, Volume 291, No. 23 for Dec. 5, 1974, John A. Parrish, M.D. et al, thus report a method involving oral administration of 8-methoxypsoralen (8-MOP) to a patient who is thereafter treated by exposure to a high intensity longwavelength ultraviolet light source, i.e. to a source of ultraviolet radiation in the UVA wavelength region, and preferably in the wavelength range between about 3200 and 4000 Angstroms, with a peak emission at about 3650 Angstroms. The highly successful treatment is deemed to be effective by interrupting the disease process in psoriasis, a disorder characterized by an accelerated cell cycle and rate of DNA synthesis. The treatment acts to inhibit DNA synthesis by formation of C-4 cyclo-addition products between the pyrimidine bases of the nucleic acids and psoralen molecule. Since the 5,6 double bond of the pyrimidine can photoreact with the psoralen molecule at either the 3,4 double bond of the pyrone ring or at the 4',5' double bond of the furan ring, two types of photoadducts are possible. In consequence formation of photo-induced DNA cross-links is enabled.
In this sequence of treatment thus employed in the treatment of psoriasis, it has been common to place the patient following administration of the psoralen, in a light box or other environment whereat the high intensity illumination is effected. It has come to the attention of investigators that a side effect resulting from the cited treatment, can occasionally be the destruction of certain nucleated blood cells. Investigation appears to establish that such result obtains because the incident UV radiation has sufficient penetrating power, to induce some bonding between the psoralen introduced into the bloodstream and the nucleic acid of the nucleated blood cells such as the lymphocytes. In consequence the metabolic processes of such modified lymphocytes are detrimentally affected, eventually leading to the inactivation and ultimate destruction of same. This type of phenomenon has been studied in vitro, and among other places, is reported in an article by G. Lischka et al appearing in Archives for Dermatological Research, 259, 293-298 (1977). Of interest for present purposes is that the reported phenomenon is regarded as an undesirable side effect, which is incident to the beneficial results otherwise achieved during treatment of psoriasis.